Structure-activity relationships study of neolamellarin A and its analogues as hypoxia inducible factor-1 (HIF-1) inhibitors
Release Time:2019-11-06 Hits:
Indexed by: Journal Papers
Date of Publication: 2019-08-15
Journal: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Included Journals: PubMed、SCIE
Volume: 29
Issue: 16
Page Number: 2327-2331
ISSN: 0960-894X
Key Words: Anti-tumor; Hypoxia inducible factor (HIF)-1; Marine alkaloids; Neolamellarin A; Structure-activity relationship
Abstract: The novel marine pyrrole alkaloid neolamellarin A derived from sponge has been shown to inhibit hypoxia-induced HIF-1 activity. In this work, we designed and synthesized neolamellarin A and its series of derivatives by a convergent synthetic strategy. The HIF-1 inhibitory activity and cytotoxicity of these compounds were evaluated in Hela cells by dual-luciferase reporter gene assay and MIT assay, respectively. The results showed that neolamellarin A 1 (IC50 = 10.8 +/- 1.0 mu M) and derivative 2b (IC50 = 11.9 +/- 3.6 mu M) had the best HIF-1 inhibitory activity and low cytotoxicity. Our SAR research focused on the effects of key regions aliphatic carbon chain length, aromatic ring substituents and C-7 substituent on biological activity, providing a basis for the subsequent research on the development of novel pyrrole alkaloids as HIF-1 inhibitors and design of small molecule probes for target protein identification.